Motion effects on SUV and lesion volume in 3D and 4D PET scanning.

To assess the effect of lesion motion and respiration rate on Standardised Uptake Value (SUV) and the ability of 4D PET to restore any loss in SUV and distortion of lesion volume on two PET/CT systems. A Perspex phantom with four cylindrical reservoirs filled with (18)F-FDG was used in this study. The cylinders measured 5, 10, 15, and 20 mm in diameter. A GE Discovery STE8 (GE Medical Systems Milwaukee, WI) and a Siemens Biograph 64/40 (Siemens Medical Solutions, Erlangen, Germany) scanner was used to acquire a stationary un-gated PET scan of the phantom. Multiple 10 min list mode 4D PET scans were acquired using the Varian RPM on the GE camera and the Anzai Gating system on the Siemens camera. The phantom was scanned at five different respiratory rates and motion amplitudes in a sinusoidal fashion, 15 RPM/1 cm, 15 RPM/2 cm, 15 RPM/4 cm, 30 RPM/2 cm and 7.5 RPM/2 cm (RPM-respirations per minute). Each scan was reconstructed into ten bins and as an un-gated static image. The SUVmax, SUVmean and volume were measured for all four reservoirs using Siemens TrueD analysis software. With increasing lesion movement the SUVmax and SUVmean decreased and the volume increased with the SUVmax in the smallest lesion underestimated by up to a factor of four. The SUVmax, SUVmean and volume were mostly recovered using 4D imaging regardless of amount of lesion displacement. The larger lesions showed better count recovery and volume correction than the smaller lesions. The respiratory rate had no effect of SUV or volume. Un-gated imaging of moving lesions decreases apparent SUV in small lesions significantly and overestimates volumes. 4D PET scanning recovers most of the apparent loss in SUV and distortion of volumes.

Comparison of CT and positron emission tomography/CT coregistered images in planning radical radiotherapy in patients with non-small-cell lung cancer.

Imaging with F-18 fluorodeoxyglucose positron emission tomography (PET) significantly improves lung cancer staging, especially when PET and CT information are combined. We describe a method for obtaining CT and PET images at separate acquisitions, which allows coregistration and incorporation of PET information into the radiotherapy (RT) planning process for non-small-cell lung cancer. The influence of PET information on RT planning was analysed for 10 consecutive patients. Computed tomography and PET images were acquired with the patient in an immobilization device, in the treatment position. Using specially written software, PET and CT data were coregistered using fiducial markers and imported into our RT planning system (Cadplan version 6). Treatment plans were prepared with and without access to PET/CT coregistered images and then compared. PET influenced the treatment plan in all cases. In three cases, geographic misses (gross tumour outside planning target volume) would have occurred had PET not been used. In a further three cases, better planning target volume marginal coverage was achieved with PET. In four patients, three with atelectasis, there were significant reductions in V20 (percentage of the total lung volume receiving 20 Gy or more). Use of coregistered PET/CT images significantly altered treatment plans in a majority of cases. This method could be used in routine practice at centres without access to a combined PET/CT scanner .

Activation of dynamin II by POPC in giant unilamellar vesicles: a two-photon fluorescence microscopy study.

The interaction of dynamin II with giant unilamellar vesicles was studied using two-photon fluorescence microscopy. Dynamin II, labeled with fluorescein, was injected into a microscope chamber containing giant unilamellar vesicles, which were composed of either pure 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or a mixture of POPC and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). Binding of the fluorescent dynamin II to giant unilamellar vesicles, in the presence and absence of PI(4,5)P2, was directly observed using two-photon fluorescence microscopy. This binding was also visualized using the fluorescent N-methylanthraniloyl guanosine 5'-[gamma-thio]triphosphate analogue. The membrane probe 6-dodecanoyl-2-dimethylamine-naphthalene was used to monitor the physical state of the lipid in the giant unilamellar vesicles in the absence and presence of dynamin. A surprising finding was the fact that dynamin II bound to vesicles in the absence of PI(4,5)P2. Activation of the GTPase activity of dynamin II by pure POPC was then shown.

Display of positron emission tomography with Cadplan.

Recent clinical experience at Peter MacCallum Cancer Institute (PMCI) with the use of unregistered Positron Emission Tomography (PET) images for radiotherapy target marking in the lung suggests that co-registered PET images would be invaluable. PMCI has three radiotherapy treatment planning systems but none of them currently is able to display or co-register PET images with Computed Tomography (CT) images. This paper details the approach taken to display co-registered PET images with the CADPLAN treatment planning system. CT Image files are normally transferred to Cadplan by DICOM transfer, but the Cadplan DICOM server will not receive (has no presentation context for) PET images. The fundamental design of the CADPLAN system envisages display of only a single image dataset, which must be a CT scan for planning reasons. The problem of data transfer is crudely solved by File Transfer Protocol (FTP) over the network. Fortunately the multislice format of the PET image files makes individual transfer manageable. A menu based C program running at the same time as Cadplan is invoked to sample the DICOM PET Image and create multiple Cadplan CART image format files that are co-registered with each existing transverse CT slice. With the Cadplan in contour mode, the program allows the co-registered PET images to be swapped in and out of the image section of the CART files promptly, while keeping the contour information. This allows radiotherapy target volumes to be marked using transverse PET emission images, and effectively circumvents the design constraints prohibiting the display of more than one image set. Contours can be over-laid for review on reconstructed sagittal or coronal views of CT or PET images constructed using the standard Cadplan tools. Co-registration is facilitated by identical positioning with the aid of lasers and FDG loaded fiducial markers on the PET scanner and CT couch. A polyurethane cast fixed with EFFILOCK is used to ensure identical patient orientation on the CT and PET couches. Since both imaging modalities are without significant geometric distortion the co-registration is then simply a translation. PET transmission images can be used for co-registration verification. The practical implementation of display of PET images with CADPLAN has enabled us to begin a trial of 10 patients, the results of which will be reported separately.

Performance of sodium iodide based (18)F-fluorodeoxyglucose positron emission tomography in the characterization of indeterminate pulmonary nodules or masses.

The purpose of this study was to document the accuracy of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) with sodium iodide detectors in characterizing indeterminate lung nodules or masses and in identifying additional extra-lesional findings. 50 consecutive patients without a confident diagnosis of malignancy on CT underwent (18)FDG PET with and without attenuation correction. The diagnosis of malignancy was made using visual diagnostic criteria, and tumour-to-blood pool ratios were calculated. The final diagnosis was established by surgery, biopsy or long-term follow-up. Any additional findings made at PET were recorded and similarly verified. Using blinded visual diagnostic criteria for the differentiation of malignant from benign nodules, sodium iodide PET achieved a sensitivity of 91% (30 of 33 cases), a specificity of 88% (15 of 17 cases), a positive predictive value for malignancy of 94% (30 of 32 cases) and a negative predictive value of 83% (15 of 18 cases). False positives occurred with active tuberculosis and sarcoidosis. False negatives were a 3 cm bronchoalveolar carcinoma, a 1.3 cm sarcoma metastasis and a 1 cm carcinoma. Use of tumour-to-blood pool ratios did not improve performance. PET suggested the presence of nodal or distant metastases in 13 of 33 patients with a malignant pulmonary lesion. These PET findings were confirmed in 11 patients. These results indicate that sodium iodide PET is an accurate tool for the characterization of indeterminate pulmonary masses or nodules and simultaneously provides non-invasive staging information that can alter patient management in up to one-third of such patients. Performance of sodium iodide PET is comparable with reported results for PET scanners using other detector materials.

Positron emission tomography in pulmonary masses where tissue diagnosis is unhelpful or not possible.

OBJECTIVE: To document the usefulness of positron emission tomography (PET) in diagnosing lung masses where tissue diagnosis is not possible or is unhelpful. DESIGN: Cohort study (partly retrospective). SETTING: Departments of positron emission tomography and diagnostic imaging of a tertiary referral dedicated cancer hospital in Melbourne. PATIENTS: 40 of 60 consecutive patients referred for evaluation of an indeterminate lung nodule or mass, comprising 15 in whom biopsy was not possible and 25 in whom biopsy had either failed or did not confirm malignancy or a specific benign diagnosis. MAIN OUTCOME MEASURES: Accuracy of blinded reading of PET scans in determining whether the lung lesion is benign or malignant (final diagnosis established either through surgical biopsy or from long term clinical and imaging follow-up). RESULTS: PET yielded 23 true positives, 13 true negatives, 3 false positives (2 tuberculosis, 1 sarcoidosis) and 1 false negative (an adenocarcinoma), giving a sensitivity of 96%, a specificity of 81%, a negative predictive value of 93%, and a positive predictive value of 88% (for malignancy). CONCLUSIONS: For lung nodules where tissue diagnosis was not possible or was unhelpful, the negative predictive power of PET was sufficiently high to avoid open biopsy, and to follow such patients with serial surveillance. On the other hand, most lesions that were positive on PET were either malignant or required specific active management determined from histological characterisation. PET therefore contributed to improved patient management and has reduced the need for open thoracotomy.

Dynamin GTPase domain mutants block endocytic vesicle formation at morphologically distinct stages.

Abundant evidence has shown that the GTPase dynamin is required for receptor-mediated endocytosis, but its exact role in endocytic clathrin-coated vesicle formation remains to be established. Whereas dynamin GTPase domain mutants that are defective in GTP binding and hydrolysis are potent dominant-negative inhibitors of receptor-mediated endocytosis, overexpression of dynamin GTPase effector domain (GED) mutants that are selectively defective in assembly-stimulated GTPase-activating protein activity can stimulate the formation of constricted coated pits and receptor-mediated endocytosis. These apparently conflicting results suggest that a complex relationship exists between dynamin's GTPase cycle of binding and hydrolysis and its role in endocytic coated vesicle formation. We sought to explore this complex relationship by generating dynamin GTPase mutants predicted to be defective at distinct stages of its GTPase cycle and examining the structural intermediates that accumulate in cells overexpressing these mutants. We report that the effects of nucleotide-binding domain mutants on dynamin's GTPase cycle in vitro are not as predicted by comparison to other GTPase superfamily members. Specifically, GTP and GDP association was destabilized for each of the GTPase domain mutants we analyzed. Nonetheless, we find that overexpression of dynamin mutants with subtle differences in their GTPase properties can lead to the accumulation of distinct intermediates in endocytic coated vesicle formation.

Combined magnetic resonance imaging and single-photon emission tomography scanning in the discrimination of Alzheimer's disease from age-matched controls.

OBJECTIVE: To compare the utility of temporal lobe magnetic resonance imaging (MRI) and single-photon emission tomography (SPET) scanning in discriminating between subjects with Alzheimer's disease (AD) and age-matched controls. METHODS: Thirty subjects with NINCDS-ADRDA AD (23 probable AD, 5 possible AD, 2 definite AD) and 22 age- and sex-matched controls underwent T1-weighted coronal MRI scanning (0.3 T) and technetium 99m-HMPAO SPET scanning. MRI scans were analyzed using a digitizer system with volumes of hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, and whole cerebral cortex calculated. From SPET scans, regional cerebral blood flow (rCBF) was assessed in anterior and posterior frontal, parietal, occipital, and mesial temporal cortex using a region of interest analysis with the cerebellum as a reference area. RESULTS: Using MRI, the areas that best separated groups were left hippocampal and left amygdala volume, resulting in correct classification (patient vs. control) in 79% of cases (sensitivity 77%, specificity 82%). Exactly the same proportion of subjects were correctly classified by SPET, with the most discriminating rCBF changes being left parietal and right posterior frontal. Combining information from both scans improved the proportion of correctly classified subjects in a discriminant function to 90% (sensitivity 93%, specificity 86%; only 2 AD and 3 controls misclassified). All AD subjects had abnormalities on MRI and/or SPET (sensitivity for combined examinations 100%), while abnormalities on both MRI and SPET had a positive predictive value of 100% for dementia (including the detection of one control subject who later had dementia). Significant correlations between MRI and SPET measures were seen in control subjects but not in patients. CONCLUSION: Both 0.3 T MRI and single rotating gamma camera SPET were equally useful in separating AD subjects from age-matched controls, although the combination of both significantly enhanced discrimination. In particular, all AD subjects had abnormalities on either MRI or SPET and both techniques may have an important role in assisting with clinical diagnosis, though replication in other centers and examination of differentiation of AD from other causes of dementia need to be examined.

The utility of a 3-dimensional, large-field-of-view, sodium iodide crystal--based PET scanner in the presurgical evaluation of partial epilepsy.

UNLABELLED: (18)F-FDG PET is an accurate and reliable technique for localizing medically refractory temporal lobe epilepsy, but widespread use has been hindered by limited reimbursement in many countries because of the high cost of traditional PET equipment and radioisotopes. Additionally, the place of FDG PET as a cost-effective tool for presurgical evaluation of epilepsy has been questioned because of limited data showing that FDG PET provides localization information incremental to that provided by more established techniques, particularly MRI and ictal electroencephalography (EEG). Three-dimensional (3D), large-field-of-view, sodium iodide crystal-based scanners have lower equipment and running costs and better multiplanar resolution than traditional 2-dimensional bismuth germinate (BGO) systems but have not yet been validated for evaluation of epilepsy. Our purpose was to investigate the localization rate, accuracy, and prognostic value of FDG PET images acquired on a 3D, large-field-of-view, sodium iodide crystal-based PET scanner in the presurgical evaluation of intractable partial epilepsy. We also wanted to establish the incremental value of FDG PET over established MRI and ictal EEG techniques. METHODS: Fifty-five patients who were surgical candidates because of medically refractory partial epilepsy were examined. For most of these patients, the lesions had not been clearly localized on conventional assessment. The FDG PET scans were reviewed independently by 2 reviewers who were unaware of the patients' clinical details, ictal EEG findings, and volumetric MRI results, and the FDG PET results were correlated with those of MRI and EEG and with postsurgical outcome. RESULTS: Forty-two patients (76%) had localizing FDG PET images (37 temporal, 5 extratemporal). The ictal EEG recordings were localizing in 66%, and the MRI findings were localizing in 27% (which increased to 35% after the MRI findings were reviewed again after PET). Concordance between the site of the PET localizations and the site of the MRI or EEG localizations was 100%. The PET images were localizing in 63% and 69% of patients with nonlocalizing ictal EEG and MRI findings, respectively. Twenty-one of 24 patients who subsequently underwent epilepsy surgery had localizing FDG PET images; of these 21 patients, 18 (86%) had a class I outcome. Multiple regression analysis showed the FDG PET results to be predictive of postsurgical outcome independently of the MRI findings. CONCLUSION: For intractable partial epilepsy, FDG PET using a 3D, large-field-of-view, sodium iodide crystal-based scanner provided clinically useful localizing information that was at least as accurate as the results reported for traditional BGO-based scanners. The PET images provided prognostically significant localization information incremental to that provided by volumetric MRI and ictal EEG, particularly if 1 of these studies was nonlocalizing.

Pattern of uptake and excretion of (18)F-FDG in the lactating breast.

UNLABELLED: Excretion of radiopharmaceuticals into breast milk poses a potential risk to infants and clear recommendations regarding interruption times are required. There are few data available regarding the impact of (18)F-FDG on this issue. With increasing use of PET for oncologic imaging and its potential advantages to nursing mothers because of its short physical half-life compared with other commonly used tumor imaging agents such as (67)Ga and (201)Tl, evaluation of the excretion pattern of this agent in breast milk is important. METHODS: We have evaluated the uptake of FDG in the breasts in 7 women, 6 of whom were lactating and 1 of whom was in early postpartum but had not commenced breast-feeding. Milk samples were obtained from 4 of the lactating women, including serial samples from 1. RESULTS: Significantly increased breast uptake was identified in all lactating breasts but not in 1 breast consistently refused by the nursing infant or in the woman who had not begun breast-feeding after delivery of her child. No qualitative change or semiquantitative estimate of radiotracer uptake in the breast was seen after expression of breast milk. Decay-corrected activity measurable in breast milk ranged from 5.54 to 19.3 Bq/mL/MBq injected. Using a standard model of breast-feeding, the calculated maximum cumulative dose to the infant, 0.085 mSv with no interruption of breast-feeding, is well below the recommended limit of 1 mSv. CONCLUSION: High uptake of FDG in the lactating breast appears to be related to suckling. There is, however, little secretion of activity into breast milk. Accordingly, a higher radiation dose is received by the infant from close contact with the breast than from ingestion of radioactive milk.

A novel family of phosphatidylinositol 4-kinases conserved from yeast to humans.

Phosphatidylinositolpolyphosphates (PIPs) are centrally involved in many biological processes, ranging from cell growth and organization of the actin cytoskeleton to endo- and exocytosis. Phosphorylation of phosphatidylinositol at the D-4 position, an essential step in the biosynthesis of PIPs, appears to be catalyzed by two biochemically distinct enzymes. However, only one of these two enzymes has been molecularly characterized. We now describe a novel class of phosphatidylinositol 4-kinases that probably corresponds to the missing element in phosphatidylinositol metabolism. These kinases are highly conserved evolutionarily, but unrelated to previously characterized phosphatidylinositol kinases, and thus represent the founding members of a new family. The novel phosphatidylinositol 4-kinases, which are widely expressed in cells, only phosphorylate phosphatidylinositol, are potently inhibited by adenosine, but are insensitive to wortmannin or phenylarsine oxide. Although they lack an obvious transmembrane domain, they are strongly attached to membranes by palmitoylation. Our data suggest that independent pathways for phosphatidylinositol 4-phosphate synthesis emerged during evolution, possibly to allow tight temporal and spatial control over the production of this key signaling molecule.

Clinical impact of (18)F fluorodeoxyglucose positron emission tomography in patients with non-small-cell lung cancer: a prospective study.

PURPOSE: To prospectively study the impact of (18)F fluorodeoxyglucose (FDG) positron emission tomography (PET) on clinical management of patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred five consecutive patients with NSCLC undergoing (18)F FDG PET were analyzed. Before PET, referring physicians recorded scan indication, conventional clinical stage, and proposed treatment plan. PET scan results were reported in conjunction with available clinical and imaging data, including results of computed tomography (CT). Subsequent management and appropriateness of PET-induced changes were assessed by follow-up for at least 6 months or until the patient's death. RESULTS: Indications for PET were primary staging (n = 59), restaging (n = 34), and suspected malignancy subsequently proven to be NSCLC (n = 12). In 27 (26%) of 105 of cases, PET results led to a change from curative to palliative therapy by upstaging disease extent. Validity of the PET result was established in all but one case. PET appropriately downstaged 10 of 16 patients initially planned for palliative therapy, allowing either potentially curative treatment (four patients) or no treatment (six patients). PET influenced the radiation delivery in 22 (65%) of 34 patients who subsequently received radical radiotherapy. Twelve patients considered probably inoperable on conventional imaging studies were downstaged by PET and underwent potentially curative surgery. PET missed only one primary tumor (5-mm scar carcinoma). CT and PET understaged three of 20 surgical patients (two with N1 lesions < 5 mm and one with unrecognized atrial involvement), and PET missed one small intrapulmonary metastasis apparent on CT. No pathological N2 disease was missed on PET. CONCLUSION: FDG PET scanning changed or influenced management decisions in 70 patients (67%) with NSCLC. Patients were frequently spared unnecessary treatment, and management was more appropriately targeted.

Imaging with F-18 FDG PET is superior to Tl-201 SPECT in the staging of non-small cell lung cancer for radical radiation therapy.

Thallium-201 (Tl-201) single photon emission computed tomography (SPECT) is funded for evaluation of malignancy in Australia and may have utility for staging of non-small cell lung cancer (NSCLC) if CT results are equivocal. Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) is superior to CT for staging NSCLC but is more expensive and less widely available than Tl-201 SPECT. Therefore, these techniques were prospectively compared in 27 radical radiation therapy candidates. Patients were allocated a conventional, PET and Tl-201 stage. Tumour to background ratios (TBR) were recorded for the primary on both techniques. Metastatic disease was confirmed by surgical pathology, serial imaging or clinical follow up. Tumour to background ratios were consistently higher for FDG PET than Tl-201 SPECT (P < 0.0001). Positron emission tomography detected all known primary tumours but Tl-201 failed to image four primary tumours (15%). In 10 of 18 cases of discordance between PET and Tl-201 SPECT regarding stage, corroboration was available from pathology or disease progression. Positron emission tomography was shown to have a 100% positive predictive value, including all three patients with PET-detected distant metastases (P=0.002). Results indicate that PET is superior to Tl-201 SPECT scanning in the staging of NSCLC for radical radiation therapy, and that the low sensitivity for detection of local and metastatic disease is likely to limit the clinical impact and cost-effectiveness of this technique despite its lower cost.

Occupational Exposure in Nuclear Medicine and PET.

Purpose: With the increasing use of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for scanning in oncology in our center, a radiation dose survey was performed to determine the impact on staff exposure. Conventional nuclear medicine procedures such as gallium scan, bone scans, and sestamibi cardiac scans are used for comparative purposes.Procedure: Patients were measured using a hand-held radiation monitor (Victoreen 450-P) at various distances and times that replicate typical patient contact scenarios in the Diagnostic Imaging Department.Results: We present our findings from the survey and the implications these have on staff radiation exposure. The data suggest that emerging oncologic techniques such as PET, high dose gallium-67, and high dose Tl-201 do not represent a significantly greater occupational radiation hazard than conventional nuclear medicine procedures.

The mechanism of GTP hydrolysis by dynamin II: a transient kinetic study.

Dynamin II is a 98 kDa protein (870 amino acids) required for the late stages of clathrin-mediated endocytosis. The GTPase activity of dynamin is required for its function in the budding stages of receptor-mediated endocytosis and synaptic vesicle recycling. This activity is stimulated when dynamin self-associates on multivalent binding surfaces, such as microtubules and anionic liposomes. We first investigated the oligomeric state of dynamin II by analytical ultracentrifuge sedimentation equilibrium measurements at high ionic strength and found that it was best described by a monomer-tetramer equilibrium. We then studied the intrinsic dynamin GTPase mechanism by using a combination of fluorescence stopped-flow and HPLC methods using the fluorescent analogue of GTP, mantdGTP (2'-deoxy-3'-O-(N-methylanthraniloyl) guanosine-5'-triphosphate), under the same ionic strength conditions. The results are interpreted as showing that mantdGTP binds to dynamin in a two-step mechanism. The dissociation constant of mantdGTP binding to dynamin, calculated from the ratio of the off-rate to the on-rate (k(off)/k(on)), was 0.5 microM. Cleavage of mantdGTP then occurs to mantdGDP and P(i) followed by the rapid release of mantdGDP and P(i). No evidence of reversibility of hydrolysis was observed. The cleavage step itself is the rate-limiting step in the mechanism. This mechanism more closely resembles that of the Ras family of proteins involved in cell signaling than the myosin ATPase involved in cellular motility.

cDNA cloning, expression, and functional characterization of PI31, a proline-rich inhibitor of the proteasome.

The primary structure of PI31, a protein inhibitor of the 20 S proteasome, was deduced by cDNA cloning and sequencing. The human protein has a calculated molecular weight of 29,792, a value in excellent accord with 31,000, as estimated by SDS-polyacrylamide gel electrophoresis for purified bovine PI31, and is not similar to any other protein in current data bases. PI31 is a proline-rich protein, particularly within its carboxyl-terminal half where 26% of the amino acids are proline. Wild-type PI31 and various truncation mutants were expressed in Escherichia coli and purified to homogeneity. Recombinant wild-type PI31 displayed structural and functional properties similar to those of PI31 purified from bovine red blood cells and inhibited the hydrolysis of protein and peptide substrates by the 20 S proteasome. Analysis of truncation mutants demonstrated that proteasome inhibition was conferred by the carboxyl-terminal proline-rich domain of PI31, which appears to have an extended secondary structure. Inhibition of the 20 S proteasome by PI31 involved formation a proteasome-PI31 complex. In addition to its direct inhibition of the 20 S proteasome, PI31 inhibited the activation of the proteasome by each of two proteasome regulatory proteins, PA700 and PA28. These results suggest that PI31 plays an important role in control of proteasome function, including that in ubiquitin-dependent pathways of protein degradation.

Regulation of the enzymatic and motor activities of myosin I.

Myosins I were the first unconventional myosins to be purified and they remain the best characterized. They have been implicated in various motile processes, including organelle translocation, ion channel gating and cytoskeletal reorganization but their exact cellular functions are still unclear. All members of the myosin I family, from yeast to man, have three structural domains: a catalytic head domain that binds ATP and actin; a tail domain believed to be involved in targeting the myosins to specific subcellular locations and a junction or neck domain that connects them and interacts with light chains. In this review we discuss how each of these three domains contributes to the regulation of myosin I enzymatic activity, motor activity and subcellular localization.

29. F-18 FDG PET for Suspected or Confirmed Regional Recurrence of Colon Cancer. A Prospective Study of Impact and Outcome.

Purpose: Survival of patients (pts) undergoing "curative" treatment for colorectal carcinoma remains poor. Retrospective studies suggest that F-18 FDG PET is more accurate than CT for restaging suspected recurrent disease and favourably impacts management. The aim of this study was to confirm this by prospective analysis.Patient Population and Methods: 102 consecutive patients for whom the referring clinicians had prospectively committed to a treatment plan based on conventional staging investigations and who then underwent F-18 FDG PET scanning were evaluated for management change and outcome. The accuracy of PET results was assessed by surgical findings or clinical follow-up.Results: Overall PET changed management in 66/102 (65%) pts including14 pts changed from observation to active treatment after PET localized disease and 6 pts planned for local therapy to observation after negative PET. Planned surgery was cancelled in 28 pts whereas surgery was initiated in 11 pts. Radiotherapy was prevented in 5 pts, initiated in 11 and the radiation field altered in 5 others. The accuracy of the PET results could be assessed in 63/66 (95%) pts in whom management was changed. Relapse was confirmed in 50/51 pts with a positive PET but disease extent was underestimated in 4 cases. False negative PET results were confirmed in 5 cases.Conclusion: FDG PET has a high and appropriate impact on patient management in patients with suspected recurrent disease. PET can miss small volume disease but the major benefit of PET is to prevent futile attempts at local salvage therapies.